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Human Immunodeficiency Virus (HIV)
There are two strains of HIV: * HIV 1 – common strain that mostly everyone gets. * HIV 2 – in Africa, milder strain, it progresses slowly that you can live as long as everyone else HIV 1 leads to AIDS after about 8 years of incubation. RNA retrovirus Use an enzyme called reverse transcriptase, that will take single stranded viral RNA to make double stranded viral DNA. Basic structure 2 single stranded RNA, surrounded by a capsid, which is surrounded by an envelope with spikes, which allow for adherence to WBC. There are 2 receptors on WBC that the spike can fit in. Morbidity 45 million (worldwide) are HIV+ or have AIDS. 12-15 million of those are babies (through placenta) Mortality 5% of HIV+ don’t go on to getting AIDS because of the delta 32 mutation of CCR5 gene Of the 95% who progress to AIDS, the mortality rate has dropped from 63% in 1995 to 18% in 1998. Now it’s a chronic infection, but there is no cure just yet. Transmission It is mainly transmitted through unprotected sex; semen and vaginal secretions there are 10-50 virus particles/mL. Another major way of getting this is through blood, which have 1k to 100k virus particles/mL. Lasts 6 hours in blood, 1.5 days if it's in a cell or pus. * Placenta – 30% chance of infection * Breast milk – 4% chance of infection Saliva, sweat, tears, tomit, feces and urine are not considered methods of transmission because there are less than 1 virus particle/mL (but don't risk it). Period of Incubation 8 years on avgerage. It is considered AIDS when your CD4 cells' number drops from >500 cells/mL to <200 cells/mL Stages of Infection The first stage, category A, lasts for the first 3 years. When you first get infected, your dendritic cells (WBC) attack the virus. For the first 2-3 weeks, you get symptoms similar to mono, but even when that goes away you are still HIV+, have a viremia, and can spread it to others. The second stage, category B, last during the years 4 through 8, and patients are mildly symptomatic. Lymph nodes are constantly swollen, and candida infections occur in the mouth. The final stage, category C, is also known as AIDS. It occurs after the CD4 cell count drops to under 200cells/mL, and is characterized by frequent diarrhea and weight loss, as well as other infections. Main bacterial infection: Mycobacterium avium intracellular complex Viruses: Herpes Zoster, Herpes Simplex, CMV disseminated Protozoa: Toxoplasmosis (Infectious through cat feces) is the most common cause of encephalitis in AIDS patients, which can lead to brain damage and mental retardation. Fungi: Candida albicans, Pneumocystis jiroveci pneumonia (PCP)(used to be main killer of AIDS patients), cryptococcus neoformans (meningitis in SE Asians), and Penicillium marneffei. Treatment Lifecycle of AIDS: # Adsorption – when the HIV hooks onto CD4 cell receptors with spikes # Penetration (Fusion) – after successfully hooking onto WBC, the virus has to pass through the cell membrane # Replication – nucleic acid has to get out of the envelope & capsid to replicate itself. Single stranded viral RNA to make double stranded viral DNA # Maturation – take the single stranded RNA & put it inside a capsid (putting things together) # Release (budding) – put capsid inside envelope and add spikes, exit cells To Prevent Adsorption Maraviroc (MVC) – binds onto ONLY CCR5 co-receptors & make it non-functional, preventing HIV strain from binding to CCR5 coreceptor. But some HIV strains use CXCR4 coreceptors. Maraviroc not approved for those strains. To Prevent Penetration (Fusion Inhibitor) Enfuvirtide (ENF or Fuzeon) attaches to GP-41 (glycoprotein 41) of virus, preventing it from passing the cell membrane. To Prevent Replication NaRTI/ NRTI, Nucleoside (Analogue) Reverse Transcriptase Inhibitor, are nucelotide analogues that competitvely inhibit reverse transcriptase. Examples include, Azidothymidine, which mimics Thymine and is used to prevent the spread of AIDS from the mother to the child, Lamivudine, Emtricitabine, and Tenofovir NNRTI, or non-nucleotide analogue reverse transcriptase inhibitor include Efavirenz (EFV) and Nevirapine (NVP) To prevent maturation Protease inhibitors: Indinavir (IDV), ritonavir (RTV) To prevent budding/release Interferon HAART (Highly Active Anti-Retroviral Treatment) (Cocktail of 3+ Drugs) For treatment-naïve patients, Tenofovir (NRTI), Emtricitabine (NRTI), & Efavirenz (NNRTI) are given. Advantage: Decrease the viral replication (lower virus particle #) & chance of mutation. Increase CD4 WBC cell count (stronger immune system)